Proinflammatory Effects of C-Peptide in Different Tissues

Vasic, Dusica; Walcher, Daniel

doi:10.1155/2012/932725

Cited by 16 publications

(15 citation statements)

References 45 publications

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“…However, recent studies have revealed that it displays various functions in different cell types, although its receptor is unknown. These functions include binding to the pertussis-toxin-sensitive G-protein-coupled receptor on Swiss 3T3 fibroblasts, activation of the p38 protein kinase pathway in mouse lung capillary endothelial cells and activation of Na+/K+-ATPase in renal tubule segments [ 29 ]. At physiological concentrations, C-peptide seems to have a positive effect on chronic complications associated with T1DM, such as diabetic neuropathy and endothelial dysfunction, by providing protection against glucose-induced endothelial apoptosis.…”

Section: Discussionmentioning

confidence: 99%

C-Peptide Is Independently Associated with an Increased Risk of Coronary Artery Disease in T2DM Subjects: A Cross-Sectional Study

Wang

Lin

et al. 2015

PLoS ONE

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ObjectiveC-peptide has been reported to be a marker of subclinical atherosclerosis in type 2 diabetes mellitus (T2DM) patients, whereas its role in coronary artery disease (CAD) has not been clarified, especially in diabetics with differing body mass indices (BMIs).Design and MethodsThis cross-sectional study included 501 patients with T2DM. First, all subjects were divided into the following two groups: CAD and non-CAD. Then, binary logistic regression was used to determine the risk factors for CAD for all patients. To clarify the role of obesity, we re-divided all subjects into two additional groups (obese and non-obese) based on BMI. Finally, binary logistic regression was used to determine the risk factors for CAD for each weight group.ResultsThe patients with CAD showed a higher BMI and fasting C-peptide level in addition to an increased prevalence of traditional risk factors for CAD, such as hypertension, insulin resistance, higher cholesterol, cysteine-C (Cys-C) and lower estimated glomerular filtration rate (eGFR). Logistic regression analysis showed that fasting C-peptide (OR=1.513, p=0.005), insulin treatment (OR=1.832, p=0.027) hypertension (OR=1.987, p=0.016) and hyperlipidemia (OR=4.159, p<0.001) significantly increased the risk of clinical CAD in the T2DM patients independent of age, gender, diabetes duration, smoking and alcohol statuses, fasting insulin and glucose, hypoglycemic episodes, UA and eGFR. Additionally, in both of the obese (OR=1.488, p=0.049) and non-obese (OR=1.686, p=0.037) DM groups, C-peptide was associated with an increased risk of CAD after multiple adjustments.ConclusionsC-peptide is associated with an increased CAD risk in T2DM patients, no matter whether they are obese or not.

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Section: Discussionmentioning

confidence: 99%

C-Peptide Is Independently Associated with an Increased Risk of Coronary Artery Disease in T2DM Subjects: A Cross-Sectional Study

Wang

Lin

et al. 2015

PLoS ONE

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“…The start of hyperinsulinemia at the pre-IGT stage is an important and critical issue for early clinical care and prevention of long-term complication of type 2 diabetes mellitus. C-peptide, a structure cleaved from proinsulin, is equimolar with insulin and can bind to different cell receptors activating signaling pathways (6). It can deposit in the vascular walls of diabetic individuals and bring about pro-infl ammatory effect leading to atherogenesis (7).…”

Section: Discussionmentioning

confidence: 99%

Correlation of Glycosylated Hemoglobin And Oral Glucose Tolerance Test Results In Hyperinsulinemic Pre-Impaired Glucose Tolerance State Versus Normoinsulinemic-Normal OGTT

Torres-Salvador¹,

Malaza²,

Mercado-Asis³

2018

jmust

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Background Prediabetes is an intermediate stage prior to development of diabetes mellitus. Preimpaired glucose tolerance state represents an early stage in the pathogenesis of diabetes wherein the normal glucose is attained by compensated hyperinsulinemia. Glycosylated hemoglobin is used in diagnosis and monitoring of diabetes but has not been explored in pre-IGT state. The objective of this study is to compare the 2-hour blood glucose, 2-hour insulin level, and HbA1c between normoinsulinemic-normal OGTT and pre-IGT groups. Methods Conducted at University of Santo Tomas Hospital, this was a retrospective analytical study of Correlation of Glycosylated Hemoglobin And Oral Glucose Tolerance Test Results levels. This suggests that indeed the metabolic abnormality must be addressed as early as the pre-IGT stage.

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“…That we did not include a pooled change from baseline analysis in our protocol could be seen as a limitation, but in order to perform this calculation we would have had to impute a standard deviation of the change, since this was not presented in the individual studies, and this may have introduced error into the results [ 12 ]. Several narrative reviews have been written on the physiological role of C-peptide and its effects on the kidney, peripheral nerves, vasculature, and inflammation, as well as its impact on intracellular signal transduction pathways in a variety of pathophysiological disease states [ 3 , 4 , 35 – 37 ]. Interestingly, the role of C-peptide in the setting of type 2 diabetes has not been well characterized.…”

Section: Discussionmentioning

confidence: 99%

C-peptide as a Therapy for Kidney Disease: A Systematic Review and Meta-Analysis

et al. 2015

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C-peptide has intrinsic biological activity and may be renoprotective. We conducted a systematic review to determine whether C-peptide had a beneficial effect on renal outcomes. MEDLINE, EMBASE, and the Cochrane Central Databases were searched for human and animal studies in which C-peptide was administered and renal endpoints were subsequently measured. We identified 4 human trials involving 74 patients as well as 18 animal studies involving 35 separate experiments with a total of 641 animals. In humans, the renal effects of exogenously delivered C-peptide were only studied in type 1 diabetics with either normal renal function or incipient nephropathy. Pooled analysis showed no difference in GFR (mean difference, -1.36 mL/min/1.73 m2, p = 0.72) in patients receiving C-peptide compared to a control group, but two studies reported a reduction in glomerular hyperfiltration (p<0.05). Reduction in albuminuria was also reported in the C-peptide group (p<0.05). In diabetic rodent models, C-peptide led to a reduction in GFR (mean difference, -0.62 mL/min, p<0.00001) reflecting a partial reduction in glomerular hyperfiltration. C-peptide also reduced proteinuria (mean difference, -186.25 mg/day, p = 0.05), glomerular volume (p<0.00001), and mesangial matrix area (p<0.00001) in diabetic animals without affecting blood pressure or plasma glucose. Most studies were relatively short-term in duration, ranging from 1 hour to 3 months. Human studies of sufficient sample size and duration are needed to determine if the beneficial effects of C-peptide seen in animal models translate into improved long-term clinical outcomes for patients with chronic kidney disease. (PROSPERO CRD42014007472)

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Proinflammatory Effects of C-Peptide in Different Tissues

Cited by 16 publications

References 45 publications

C-Peptide Is Independently Associated with an Increased Risk of Coronary Artery Disease in T2DM Subjects: A Cross-Sectional Study

C-Peptide Is Independently Associated with an Increased Risk of Coronary Artery Disease in T2DM Subjects: A Cross-Sectional Study

Correlation of Glycosylated Hemoglobin And Oral Glucose Tolerance Test Results In Hyperinsulinemic Pre-Impaired Glucose Tolerance State Versus Normoinsulinemic-Normal OGTT

C-peptide as a Therapy for Kidney Disease: A Systematic Review and Meta-Analysis

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